This invention relates to chewable dentifrice compositions and, more particularly, to chewable antiseptic dentifrice compositions wherein hypothiocyanate, a bacterial inhibitor, is produced in situ during oral chewing of the dentifrice.
The term "chewable dentifrice" as used herein refers to chewing gum, and chewable and orally soluble tablets, troches, lozenges, drops and the like.
Non-chewable dentifrices, in powder, paste, cream and liquid forms, are used for both cosmetic and therapeutic purposes. Consistent with these purposes, such dentifrices are formulated to contain active ingredients such as cleansing and polishing materials, as well as various antibacterial and anticaries agents for use as aids in the prevention of tooth decay. It is also suggested in the prior art that chewable dentifrices such as chewing gum and chewable tablets and lozenges be formulated with antiseptic-type compositions for beneficially effecting dental care.
It is generally understood in the dental art that certain kinds of tooth decay are initiated by acid etching of the tooth enamel with the source of the acid being a metabolite resulting from bacterial and enzymatic action on food particles in the oral cavity. It is generally accepted that plaque--which is a soft accumulation on the tooth surfaces consisting of an organized structure of microorganisms, proteinaceous and carbohydrate substances, epithelial cells, and food debris--is a contributory factor in the development of various pathological conditions of the teeth and soft tissue of the oral cavity. It has been suggested that the saccharolytic organisms of the oral cavity, which are associated with the plaque, cause decalcification beneath the plaque matrix through metabolic activity which results in the accumulation and localized concentration of organic acids. The etching and decalcification of the enamel may continue until the pulp chamber of the tooth is reached.
A wide variety of materials have been considered for use as decay-preventative agents in dentrifice compositions. Some of the substances which have been so considered include para-aminobenzoic acid, a combination of urea and urease to produce ammonia during oral application of the dentifrice, chlorophyll, perfluorinated long chain organic compounds, complex iodine, penicillin, benzohydroxamic acid, and glucose oxidase to produce hydrogen peroxide during oral application of the dentrifice. Substances which have been considered in connection with chewable dentifrices include: carbolic acid, menthol, thymol and eucalypthus; peroxides and perborates such as calcium peroxide and sodium perborate; and glucose oxidase, an oxidoreductase enzyme, to produce hydrogen peroxide during oral chewing of the dentifrice.
U.S. Pat. No. 1,171,392 (Meier, 1916) discloses an antiseptic chewing gum comprising chicle, glucose and sugar together with an admixture of powdered chalk and an antiseptic such as carbolic acid, menthol, thymol or eucalypthus.
U.S. Pat. No. 2,290,862 (Canning, 1942) discloses an antiseptic chewing gum comprising chicle, glucose, flavoring material and sugar together with an admixture of hydrogenated peanut oil and calcium peroxide.
Commercial glucose oxidase which also contains catalase is promoted to the food and beverage industry as an agent for protecting their suspectible packaged products against deterioration in the presence of oxygen and/or glucose by effecting an enzymatic in situ reaction which results in the consumption of oxygen and glucose with an intermediate product being hydrogen peroxide and the ultimate end product of the enzymatic reaction being gluconic acid.
U.S. Pat. No. 2,891,868 (Heggie et al., 1959) discloses that chewing gum which is formulated with an oxygen sensitive flavoring agent can be protected against oxidative deterioration of the flavoring agent by incorporating into the formulation an enzyme system containing glucose, glucose oxidase and catalase, and that this protection is effective in the presence of bound water only and does not require free water.
U.S. Pat. No. 4,178,362 (Hoogendoorn et al., 1979) discloses an enzymatic chewable dentifrice containing glucose oxidase which acts on glucose present in saliva and tooth plaque to produce hydrogen peroxide. The patentees note that oral bacteria, through enzyme systems having SH-groups, effect glycolysis of food products containing sugars and point out that lactoperoxidase, which is present in saliva, provides the means for transferring oxygen from hydrogen peroxide to the oral bacteria resulting in the oxidation of the SH-containing enzymes into inactive disulfide enzymes. It is further dislcosed that the dentifrice may be formulated with potassium thiocyanate.
U.S. Pat. No. 4,269,822 (Pellico et al., 1981) discloses an antiseptic dentifrice containing an oxidizable amino acid substrate and an oxidoreductase enzyme specific to such substrate for producing hydrogen peroxide and ammonia upon oral application of the dentifrice, with pre-application stability being maintained by limiting the quantity of any water present in the dentifrice.
Morrison et al., Biology of the Mouth, American Association for the Advancement of Science, 1968, pp. 89-110 disclose: that lactoperoxidase, sodium thiocyanate and hydrogen peroxide define a bacterial inhibitory system; that in vivo production of hydrogen peroxide might be generated by microorganisms; and that the lactoperoxidase antimicrobiological system (which also includes hydrogen peroxide and thiocyanate) is reversed by catalase, which competes with lactoperoxidase for available hydrogen peroxide.
Hoogendoorn et al., Caries Research, 11:77-84, 1977, disclose that the hypothiocyanate ion is the bacterial inhibitor formed by the system containing lactoperoxdiase, thiocyanate and hydrogen peroxide and further disclose that a high concentration of hydrogen peroxide inactivates lactoperoxdiase.
Thomas et al., Journal of Dental Research, 60(4), pp. 785-796, April, 1981, disclose with respect to the salivary antimicrobial system consisting of peroxidase enzyme(s), hydrogen peroxide and thiocyanate ion: (a) that peroxidase is synthesized by the salivary glands, (b) that production of hydrogen peroxide in saliva may be due to leucocytes or to oral bacteria primarily streptococci and lactobacilli, (c) that the salivary glands concentrate thiocyanate ion from blood and (d) that the antimicrobial activity of the peroxidase system is due to peroxidase catalyzed oxidation of thiocyanate ion (SCN) to hypothiocyanate ion (OSCN); and (e) further disclose that the yield or accumulation of hypothiocyanate from the aforesaid antimicrobial system can be increased by the presence of aminohexoses, namely, glucosamine and N-acetyl glucosamine.
The effectiveness of a glucose oxidase chewable dentifrice (U.S. Pat. No. 4,178,362) as a bacterial inhibitor through the production of hypothiocyanate is dependent, to a significant extent, upon the subsisting oral concentration of glucose, potassium thiocyanate and lactoperoxdiase as well as hydrogen peroxide at the time of oral chewing of the dentifrice. The concentration of those ingredients supplied by saliva, including potassium thiocyanate and lactoperoxdiase, varies as a direct function of biological production and salivary flow. Thus, when salivary flow is at a diminished level either as a natural event or as an event arising out of certain types of medical treatment, the oral concentration of potassium thiocyanate and lactoperoxdiase will be correspondingly reduced which, in turn, is a limiting factor in the oral production of hypothiocyanate bacterial inhibitor. Moreover, when the oral concentration of lactoperoxdiase is suppressed through diminished salivary flow, the oral concentration of hydrogen peroxide produced by the glucose oxidase/carbohydrase system, as described in U.S. Pat. No. 4,178,362, may rise to the threshold level which can impede the effectiveness of lactoperoxidiase. Accordingly, it would be advantageous to provide a substantially self-contained, hypothiocyanate generating, enzymatic chewable dentifrice which is not dependent upon the naturally occurring, oral concentration of glucose, potassium thiocyanate or lactoperoxidiase for antibacterial effectiveness, upon oral chewing of the dentifrice.